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Amyloid-associated ...
Amyloid-associated increases in soluble tau relate to tau aggregation rates and cognitive decline in early Alzheimer's disease
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- Pichet Binette, Alexa (author)
- Lund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Clinical Memory Research,Lund University Research Groups
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- Franzmeier, Nicolai (author)
- University Hospital Munich
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- Spotorno, Nicola (author)
- Lund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Clinical Memory Research,Lund University Research Groups
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- Ewers, Michael (author)
- University Hospital Munich,German Center for Neurodegenerative Diseases (DZNE), Bonn
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- Brendel, Matthias (author)
- University Hospital Munich
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- Biel, Davina (author)
- University Hospital Munich
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- Strandberg, Olof (author)
- Lund University,Lunds universitet,Medicinsk strålningsfysik, Lund,Sektion V,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,MR Physics,Medical Radiation Physics, Lund,Section V,Department of Clinical Sciences, Lund,Faculty of Medicine,Clinical Memory Research,Lund University Research Groups
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- Janelidze, Shorena (author)
- Lund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Clinical Memory Research,Lund University Research Groups
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- Palmqvist, Sebastian (author)
- Lund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Clinical Memory Research,Lund University Research Groups,Skåne University Hospital
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- Mattsson-Carlgren, Niklas (author)
- Lund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Brain Injury After Cardiac Arrest,WCMM- Wallenberg center för molekylär medicinsk forskning,Medicinska fakulteten,Clinical Memory Research,Lund University Research Groups,WCMM-Wallenberg Centre for Molecular Medicine,Faculty of Medicine,Skåne University Hospital
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- Smith, Ruben (author)
- Lund University,Lunds universitet,Neurologi, Lund,Sektion IV,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Regeneration in Movement Disorders,Neurology, Lund,Section IV,Department of Clinical Sciences, Lund,Faculty of Medicine,Clinical Memory Research,Lund University Research Groups,Skåne University Hospital
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- Stomrud, Erik (author)
- Lund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Clinical Memory Research,Lund University Research Groups,Skåne University Hospital
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- Ossenkoppele, Rik (author)
- Lund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Clinical Memory Research,Lund University Research Groups,Amsterdam UMC - Vrije Universiteit Amsterdam,Vrije Universiteit Amsterdam
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- Hansson, Oskar (author)
- Lund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Clinical Memory Research,Lund University Research Groups,Skåne University Hospital
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(creator_code:org_t)
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- 2022-11-04
- 2022
- English 1 s.
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1, s. 6635-6635
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Abstract
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- For optimal design of anti-amyloid-β (Aβ) and anti-tau clinical trials, we need to better understand the pathophysiological cascade of Aβ- and tau-related processes. Therefore, we set out to investigate how Aβ and soluble phosphorylated tau (p-tau) relate to the accumulation of tau aggregates assessed with PET and subsequent cognitive decline across the Alzheimer's disease (AD) continuum. Using human cross-sectional and longitudinal neuroimaging and cognitive assessment data, we show that in early stages of AD, increased concentration of soluble CSF p-tau is strongly associated with accumulation of insoluble tau aggregates across the brain, and CSF p-tau levels mediate the effect of Aβ on tau aggregation. Further, higher soluble p-tau concentrations are mainly related to faster accumulation of tau aggregates in the regions with strong functional connectivity to individual tau epicenters. In this early stage, higher soluble p-tau concentrations is associated with cognitive decline, which is mediated by faster increase of tau aggregates. In contrast, in AD dementia, when Aβ fibrils and soluble p-tau levels have plateaued, cognitive decline is related to the accumulation rate of insoluble tau aggregates. Our data suggest that therapeutic approaches reducing soluble p-tau levels might be most favorable in early AD, before widespread insoluble tau aggregates.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Neurologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Neurology (hsv//eng)
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- ref (subject category)
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- By the author/editor
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Pichet Binette, ...
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Franzmeier, Nico ...
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Spotorno, Nicola
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Ewers, Michael
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Brendel, Matthia ...
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Biel, Davina
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Strandberg, Olof
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Janelidze, Shore ...
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Palmqvist, Sebas ...
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Mattsson-Carlgre ...
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Smith, Ruben
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Stomrud, Erik
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Ossenkoppele, Ri ...
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Hansson, Oskar
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Neurology
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Nature Communica ...
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Lund University